Molecular basis for condensin targeting to chromosomal loci [Hi-C]

Faithful chromosome segregation requires packaging of the genome on both global and local scales. Condensin plays a crucial role at pericentromeres to resist spindle forces and ensure the oriented attachment of kinetochores to microtubules at mitosis. Here we demonstrate that budding yeast condensin is recruited to pericentromeres through a direct interaction between its Ycg1 subunit and the pericentromeric adaptor protein, shugoshin (Sgo1). We identify a Short Linear Motif (SLiM), termed CR1, within the C-terminal region of Sgo1 which inserts into a conserved pocket on Ycg1. Disruption of this interface abolishes the Sgo1-condensin interaction, prevents condensin recruitment to pericentromeres and results in defective sister kinetochore biorientation in mitosis. Similar motifs to CR1 are found in known and potential condensin binding partners and the Ycg1 binding pocket is broadly conserved, including in mammalian CAP-G proteins. Overall, we uncover the molecular mechanism that targets condensin to define a specialized chromosomal domain.精准染色体分离需要在全局与局部尺度对基因组进行三维包装。凝缩蛋白（condensin）在着丝粒周边区域发挥关键作用，以抵御纺锤体拉力，并确保有丝分裂过程中动粒（kinetochores）与微管的定向附着。本研究证实，出芽酵母（budding yeast）中的凝缩蛋白可通过其Ycg1亚基与着丝粒周边衔接蛋白保护素（shugoshin, Sgo1）的直接相互作用被招募至着丝粒周边区域。我们在Sgo1的C端区域鉴定出一段被命名为CR1的短线性基序（Short Linear Motif, SLiM），该基序可嵌入Ycg1上的保守口袋。该相互作用界面的破坏会阻断Sgo1与凝缩蛋白的结合，阻止凝缩蛋白被招募至着丝粒周边区域，并导致有丝分裂中姐妹动粒双向定向异常。在已知及潜在的凝缩蛋白结合伴侣中，均发现了与CR1相似的基序；且Ycg1结合口袋在进化上广泛保守，包括哺乳动物CAP-G蛋白在内。综上，本研究揭示了将凝缩蛋白靶向定位至特化染色体结构域的分子机制。